Francisella tularensis, a facultative intracellular pathogen, causes significant disease including classic ulceroglandular tularemic infection and the more deadly pulmonary tularemic infection with dissemination and tularemia. Immunity to this potential bioterrorist agent is unclearbut it appears both humoral and cell mediated immunity play a role. The purpose of this project is to investigate the potential protective efficacy of anti-Francisella vaccines consisting of Francisella capsular polysaccharide or LPS derived oligosaccharides. As these antigens are classic T-cell independent antigens, the humoral immune response towards these antigens shall be optimized by inducing a T-cell dependent response by 1) either combining these antigens with the vaccine adjuvant, meningococcal porin PorB, or conjugating the antigens to the classic vaccine carrier, tetanus toxoid or 2) convert the epitopes of F-CPS or F-OS to protein based peptide mimotopes. Both these methods are state of the art and have proven to be effective in increasing the efficacy of polysaccharide based vaccines. Most, if not all, effective anti-bacterial vaccines consist of bacterial capsular polysaccharides and this approach has great potential in inducing protection. The aims of this proposal are 1) Preparation of the Francisella capsular polysaccharide (F-CPS) and Francisella LPS derived oligosaccharide (F-OS) vaccine immunogens (combined with various adjuvants), immunization of mice and determination of anti-Francisella IgG levels, 2) Development of F-CPS and F-OS protein mimotpes and optimization of vaccine preparations based on the peptide mimotopes consensus sequences and measurement of IgG antibodies induced by this method that recognize native antigen and intact organism and 3) Determination of the potential protective efficacy of both set of vaccine preparations in Aims 1 and 2 by examining the functional activity of the vaccine induced sera in bactericidal assays, opsonophagocytic assays and prevention of macrophage invasion and measuring the protective effect of vaccination in the murine inhalation model of tularemia.